Drug Therapy for Myelodysplastic Syndromes

Different types of drugs might be used to treat myelodysplastic syndrome (MDS).

Chemotherapy

Chemotherapy (chemo) is the use of drugs for treating a disease such as cancer. Some chemo drugs can be swallowed as pills, while others are injected by needle into a vein or muscle. These drugs are considered systemic treatment because they enter the bloodstream and reach most areas of the body. This type of treatment is useful for diseases such as MDS that are not only in one part of the body. The purpose of the chemo is to kill the abnormal stem cells in the bone marrow and allow normal ones to grow back.

Hypomethylating agents

These types of chemo drugs affect the way certain genes inside a cell are controlled. These drugs activate some genes that help cells mature. They also kill cells that are dividing rapidly. Examples of this type of drug include:

• Azacitidine (Vidaza)
• Decitabine (Dacogen)

In some MDS patients, using one of these drugs can improve blood counts (sometimes enough so that blood transfusions aren’t needed), improve quality of life, lower the chance of getting leukemia, and even help a person live longer.

Azacitidine can be injected under the skin or into a vein (IV), often for 7 days in a row, once a month.

Decitabine is often injected into a vein (IV) over 3 hours every 8 hours for 3 days. This is repeated every 6 weeks. Decitabine can also be given by IV over an hour, each day for 5 days in a row, and repeated every 4 weeks.

A newer form of this drug, known as Inqovi, combines decitabine with cedazuridine, which helps stop the decitabine from being broken down in the digestive system. This allows the drug to be taken by mouth as a tablet, typically once a day for 5 days in a row, which is repeated every 4 weeks.

Hypomethylating agents can have some of the same side effects as standard chemo drugs (see below), but these side effects are usually milder.

A major side effect of these drugs is usually an early drop in blood cell counts, which tends to get better as the drug begins to work. Other side effects can include:

• Fever
• Nausea/vomiting
• Diarrhea or constipation
• Fatigue and weakness

Standard chemotherapy drugs

Standard chemo drugs are less useful for MDS than the hypomethylating agents, so they are not used often. But higher-risk MDS is more likely to progress to acute myeloid leukemia (AML), so some patients with these types of MDS may receive the same chemo treatment as AML patients.

The chemo drug most often used for MDS is cytarabine (ara-C). It can be given by itself at a low-dose, which can often help control the disease, but doesn’t often put it into remission.

Another option is to give the same, intense type of chemo that is used for younger patients with AML. This means giving cytarabine at a higher dose, along with other chemo drugs. This is more often used in younger, healthier patients with higher-risk forms of MDS (like MDS with excess blasts). Some of the chemo drugs that can be combined with cytarabine are:

• Idarubicin
• Daunorubicin

Other chemo drugs might be used as well.

Patients who get the higher-dose treatment are more likely to have their MDS go into remission, but they can also have more severe, even life-threatening side effects, so this treatment is typically given in the hospital. Still, this treatment may be an option for some patients with advanced MDS.

Chemo drugs can cause many side effects. These depend on the type and dose of the drugs given and how long they are taken. Common side effects include:

• Hair loss
• Mouth sores
• Loss of appetite
• Nausea and vomiting
• Low blood counts

MDS patients already have low blood counts, which often become even worse for a time before they get better.

• Low white blood cell counts lead to an increased risk of serious infections.
• Low platelet counts can lead to problems with easy bruising and serious bleeding, including bleeding into the brain or the intestine.
• Low red blood cell counts (or anemia) can lead to fatigue and shortness of breath. In people with heart problems, severe anemia can lead to a heart attack.

If a patient's blood cell counts become too low, they may need supportive therapy (including transfusions or growth factors) to help prevent or treat serious side effects. 

Most side effects from chemo will go away after treatment is finished. Your health care team can often suggest ways to lessen side effects. For example, drugs can be given to help prevent or reduce nausea and vomiting.

Chemo drugs can also affect other organs. For example:

• Idarubicin and daunorubicin can damage the heart, so they are often not given to patients who already have heart problems.
• Cytarabine can affect the brain and cause balance problems, sleepiness, and confusion. This is more common with higher doses.

If serious side effects occur, the chemo treatments may have to be reduced or stopped, at least temporarily. It's important to carefully monitor and adjust drug doses, because some of these side effects can be permanent.

Immune therapy

Immunomodulating drugs (IMiDs)

Lenalidomide (Revlimid) belongs to a class of drugs known as immunomodulating drugs (IMiDs). It seems to work well in low-grade MDS, often eliminating the need for blood transfusions, at least for a time. The drug seems to work best in people whose MDS cells are missing a part of chromosome 5 (MDS-del(5q)). But it can also help some MDS patients that do not have this abnormal chromosome.

Side effects can include:

• Lowered blood counts (most often the white cell count and platelet count)
• Diarrhea or constipation
• Fatigue and weakness

This drug can also increase the risk of serious blood clots that start in the veins in the legs (called a deep vein thrombosis, or DVT). Sometimes, part of a DVT can break off and travel to the lungs (called a pulmonary embolus, or PE), where it can cause breathing problems or even death.

This drug might also cause serious birth defects if given to pregnant women. Because of this, it's only available through a special program by the drug company.

Immune system suppression

Drugs that suppress the immune system can help some patients with lower-risk MDS. These drugs are most helpful for people with low numbers of cells in the bone marrow (called hypocellular bone marrow).

Anti-thymocyte globulin (ATG) is an antibody against a type of white blood cell called the T-lymphocyte, which helps control immune reactions. For some patients with MDS, T-lymphocytes interfere with normal blood cell production, so ATG can be helpful. ATG is given as an infusion through a vein. It must be given in the hospital because it can sometimes cause severe allergic reactions leading to low blood pressure and problems breathing.

Cyclosporine is another drug that can suppress the immune system. It can be used along with ATG to help some patients with MDS. Side effects of cyclosporine can include loss of appetite and kidney damage.

Targeted therapy

IDH inhibitor

In some people with MDS, the cancer cells have a change (mutation) in the IDH1 gene, which normally helps cells make the IDH1 protein.  Mutations in this gene can lead to an abnormal IDH1 protein, which can stop MDS cells from maturing the way they normally would.

Ivosidenib (Tibsovo) is an IDH1 inhibitor. It blocks the abnormal IDH1 protein, which seems to help the cancer cells mature into more normal cells. This drug can be used in people with advanced, previously treated MDS, if the cancer cells are found to have an IDH1 mutation. Your doctor can test your cancer cells to see if they have an IDH1 mutation.

This drug is taken by mouth, once a day.

Possible side effects of ivosidenib

Common side effects can include fatigue, nausea, vomiting, abdominal (belly) pain or swelling, diarrhea, loss of appetite, cough, low red blood cell counts (anemia), rash, and changes in lab tests showing the drug is affecting the liver.

Less common but more serious side effects can include changes in heart rhythm, pneumonia, and jaundice (yellowing of the eyes and skin).

More information about targeted therapy

To learn more about how targeted drugs are used to treat cancer, see Targeted Cancer Therapy.
To learn about some of the side effects listed here and how to manage them, see Managing Cancer-related Side Effects.